The World Health Organization declared a novel coronavirus disease (COVID-19) as a global pandemic the work has begun to combat it. Objective: The objective of the study was investigated whether can be used some biological tests as dependable biomarkers for indicating the severity of COVID-19 with a comparison between patients in urban and rural of Babylon province. Materials and Methods: One hundred and forty samples of blood (70 patients urban and 70 patients rural) were obtained from patients who had positive results and severe symptoms of COVID-19 infection were accomplished by Marjan Teaching Hospital from December/2021 to February/2022. D-dimer, ferritin and C-reactive protein (CRP) tests were performed according to (CLIA) technique. White blood cell (WBC), counting uses a fully automated hematology analyzer device.Results: The results showed a significant difference in D-dimer (P=0.000), ferritin (P=0.001) and WBC count (P=0.000) between patients in both urban and rural of Babylon province, while CRP was an insignificant difference (P=0.06).Conclusions: It can be inference the examination of D-dimer and CRP is considered as biomarkers for severity of COVID-19 patients in urban and rural. Whereas the effect of gender is not significant in all parameters. Furthermore, the results of frequency distribution of patients showed the concentrations of D-dimer and CRP in blood exceeded the approved normal value in both patients of urban and rural. Also, a lot of values of ferritin and WBC in urban patients exceeded the normal value and not exceeded in rural patients.